Chemical Biology

The Woscholski group focuses on the elucidation of phosphoinositde (PI) dependent signalling pathways, with particular emphasis on the role of 3-phosphorylated inositol lipids and their effectors. The making and breaking of these lipids is controlled by kinases and phosphatases, which all play important roles in the regulation of cellular processes leading to apoptosis, glucose uptake and proliferation. Deciphering the contribution of PI lipids towards cellular function relies on the availability of tools and techniques that can facilitate the imaging of the dynamics of PI lipids and their downstream effectors. Biological tools such as lipid recognition domains as well as other effector proteins are employed to assess the cellular levels and their impact on cellular function in a tempero-spatial fashion by fluorescence microscopy. This is complemented by the generation of novel chemical research tools in collaboration with scientists of the Institute of Chemical Biology, which are currently being tested for their applicability.

Another focus of our research is aimed at the unravelling of the role of the different phosphoinositide phosphatases in vivo . Fluorescence microscopy will be used to image these phosphatases and their substrates in the cellular environment. In particular, the cellular and molecular impact of the fatty acid sensitivity, head group recognition and catalytic properties of these enzymes is a major focus of our current research, which is aimed to address important biological and biomedical question such as the role of these phosphatases in Lowe syndrome, Cancer, Diabetes and degenerative diseases. This will involve the monitoring of cellular lipid signalling employing metabolic profiling techniques as well as imaging of downstream signalling elements and will ultimately aid the elucidation of the role of these PI phosphatases in the development of diseases and human health.

Mak LH, Woscholski R, 2015, Targeting PTEN using small molecule inhibitors., Methods Furse S, Mak L, Tate EW, et al., 2015, Synthesis of unsaturated phosphatidylinositol 4-phosphates and the effects of substrate unsaturation on SopB phosphatase activity, Organic & Biomolecular Chemistry, Vol:13, ISSN:1477-0520, Pages:2001-2011 O'Donnelly K, Zhao G, Patel P, et al., 2014, Isolation and kinetic characterisation of hydrophobically distinct populations of form I Rubisco, Plant Methods, Vol:10, ISSN:1746-4811 Murray JI, Woscholski R, Spivey AC, 2014, Highly efficient and selective phosphorylation of amino acid derivatives and polyols catalysed by 2-aryl-4-(dimethylamino)pyridine-N-oxides - towards kinase-like reactivity, Chemical Communications, Vol:50, ISSN:1359-7345, Pages:13608-13611 DOIAuthor Web LinkOpen Access Link

Woscholski R, 2014, Chemical intervention tools to probe phosphoinositide-dependent signalling, Biochemical Society Transactions, Vol:42, ISSN:0300-5127, Pages:1343-1348